Physical capacity increase in patients with heart failure is associated with improvement in muscle sympathetic nerve activity.

BACKGROUND: Exercise training improves physical capacity in patients with heart failure with reduced ejection fraction (HFrEF), but the mechanisms involved in this response is not fully understood. The aim of this study was to determine if physical capacity increase in patients HFrEF is associated with muscle sympathetic nerve activity (MSNA) reduction and muscle blood flow (MBF) increase. METHODS: The study included 124 patients from a 17-year database, divided according to exercise training status: 1) exercise-trained (ET, n = 83) and 2) untrained (UNT, n = 41). MSNA and MBF were obtained using microneurography and venous occlusion plethysmography, respectively. Physical capacity was evaluated by cardiopulmonary exercise test. Moderate aerobic exercise was performed 3 times/wk. for 4 months. RESULTS: Exercise training increased peak oxygen consumption (V̇O2, 16.1 ± 0.4 vs 18.9 ± 0.5 mL·kg-1·min-1, P < 0.001), LVEF (28 ± 1 vs 30 ± 1%, P = 0.027), MBF (1.57 ± 0.06 vs 2.05 ± 0.09 mL.min-1.100 ml-1, P < 0.001) and muscle vascular conductance (MVC, 1.82 ± 0.07 vs 2.45 ± 0.11 units, P < 0.001). Exercise training significantly decreased MSNA (45 ± 1 vs 32 ± 1 bursts/min, P < 0.001). The logistic regression analyses showed that MSNA [(OR) 0.921, 95% CI 0.883-0.962, P < 0.001] was independently associated with peak V̇O2. CONCLUSIONS: The increase in physical capacity provoked by aerobic exercise in patients with HFrEF is associated with the improvement in MSNA.

Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients: a Survey Study Across 30 Countries.

BACKGROUND: Statins are widely used to prevent cardiovascular disease (CVD). With advancing age, the risks of statins might outweigh the potential benefits. It is unclear which factors influence general practitioners' (GPs) advice to stop statins in oldest-old patients. OBJECTIVE: To investigate the influence of a history of CVD, statin-related side effects, frailty and short life expectancy, on GPs' advice to stop statins in oldest-old patients. DESIGN: We invited GPs to participate in this case-based survey. GPs were presented with 8 case vignettes describing patients > 80 years using a statin, and asked whether they would advise stopping statin treatment. MAIN MEASURES: Cases varied in history of CVD, statin-related side effects and frailty, with and without shortened life expectancy (< 1 year) in the context of metastatic, non-curable cancer. Odds ratios adjusted for GP characteristics (ORadj) were calculated for GPs' advice to stop. KEY RESULTS: Two thousand two hundred fifty GPs from 30 countries participated (median response rate 36%). Overall, GPs advised stopping statin treatment in 46% (95%CI 45-47) of the case vignettes; with shortened life expectancy, this proportion increased to 90% (95CI% 89-90). Advice to stop was more frequent in case vignettes without CVD compared to those with CVD (ORadj 13.8, 95%CI 12.6-15.1), with side effects compared to without ORadj 1.62 (95%CI 1.5-1.7) and with frailty (ORadj 4.1, 95%CI 3.8-4.4) compared to without. Shortened life expectancy increased advice to stop (ORadj 50.7, 95%CI 45.5-56.4) and was the strongest predictor for GP advice to stop, ranging across countries from 30% (95%CI 19-42) to 98% (95% CI 96-99). CONCLUSIONS: The absence of CVD, the presence of statin-related side effects, and frailty were all independently associated with GPs' advice to stop statins in patients aged > 80 years. Overall, and within all countries, cancer-related short life expectancy was the strongest independent predictor of GPs' advice to stop statins.

Association between clinical factors and self-underestimation of cardiovascular risk in subjects submitted to a routine health evaluation.

BACKGROUND: The perception of cardiovascular (CV) risk is essential for adoption of healthy behaviors. However, subjects underestimate their own risk. HYPOTHESIS: Clinical characteristics might be associated with self-underestimation of CV risk. METHODS: This is a retrospective, cross-sectional study of individuals submitted to routine health evaluation between 2006 and 2012, with calculated lifetime risk score (LRS) indicating intermediate or high risk for CV disease (CVD). Self-perception of risk was compared with LRS. Logistic regression analysis was performed to test the association between clinical characteristics and subjective underestimation of CV risk. RESULTS: Data from 5863 subjects (age 49.4 ± 7.1 years; 19.9% female) were collected for analysis. The LRS indicated an intermediate risk for CVD in 45.7% and a high risk in 54.3% of individuals. The self-perception of CV risk was underestimated compared with the LRS in 4918 (83.9%) subjects. In the adjusted logistic regression model, age (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.10-1.47 per 10 years, P = 0.001), smoking (OR: 1.99, 95% CI: 1.40-2.83, P < 0.001), dyslipidemia (OR: 1.21, 95% CI: 1.01-1.46, P = 0.045), physical activity (OR: 1.66, 95% CI: 1.36-2.02, P < 0.001), and use of antihypertensive (OR: 1.49, 95% CI: 1.15-1.92, P = 0.002) and lipid-lowering medications (OR: 2.13, 95% CI: 1.56-2.91, P < 0.001) were associated with higher chance of risk underestimation, whereas higher body mass index (OR: 0.92, 95% CI: 0.90-0.94, P < 0.001), depressive symptoms (OR: 0.46, 95% CI: 0.37-0.57, P < 0.001), and stress (OR: 0.41, 95% CI: 0.33-0.50, P < 0.001) decreased the chance. CONCLUSIONS: Among individuals submitted to routine medical evaluation, aging, smoking, dyslipidemia, physical activity, and use of antihypertensive and lipid-lowering medications were associated with higher chance of CV risk underestimation. Subjects with these characteristics may benefit from a more careful risk orientation.

Functional magnetic resonance imaging response as an early biomarker of cognitive decline in elderly patients with metabolic syndrome.

OBJECTIVES: We assessed whether potential changes in brain activation patterns of elderly individuals with metabolic syndrome (MetS) who were cognitively healthy (without mild cognitive impairment or dementia) were associated with cognitive decline in executive function in the short-term. METHOD: We analyzed 43 individuals (23 MetS, 20 controls) using a global geriatric evaluation, a neuropsychological battery, and task-related (attention) fMRI exam. Correlation analysis between the fMRI signal at baseline and cognitive impairment after 1year was based on the voxel-based Pearson coefficient, corrected for multiple comparisons. RESULTS: At baseline, MetS patients showed reduced brain response in frontal and parietal regions compared to controls. After one year, the MetS group also showed a decline in verbal fluency performance. fMRI response in the right dorsolateral prefrontal cortex and bilateral parietal lobes was negatively correlated with verbal fluency decline in the MetS group. DISCUSSION: Our results provide an early biomarker of the possible development of cognitive impairment, particularly in the executive function, of elderly individuals suffering from MetS. These findings also point to an up or down regulation which could be interpreted as compensatory mechanism for possible brain tissue burden caused by MetS.

A time-series analysis of the relation between unemployment rate and hospital admission for acute myocardial infarction and stroke in Brazil over more than a decade.

BACKGROUND: The effect of socioeconomic stressors on the incidence of cardiovascular disease (CVD) is currently open to debate. Using time-series analysis, our study aimed to evaluate the relationship between unemployment rate and hospital admission for acute myocardial infarction (AMI) and stroke in Brazil over a recent 11-year span. METHODS AND RESULTS: Data on monthly hospital admissions for AMI and stroke from March 2002 to December 2013 were extracted from the Brazilian Public Health System Database. The monthly unemployment rate was obtained from the Brazilian Institute for Applied Economic Research, during the same period. The autoregressive integrated moving average (ARIMA) model was used to test the association of temporal series. Statistical significance was set at p<0.05. From March 2002 to December 2013, 778,263 admissions for AMI and 1,581,675 for stroke were recorded. During this time period, the unemployment rate decreased from 12.9% in 2002 to 4.3% in 2013, while admissions due to AMI and stroke increased. However, the adjusted ARIMA model showed a positive association between the unemployment rate and admissions for AMI but not for stroke (estimate coefficient=2.81±0.93; p=0.003 and estimate coefficient=2.40±4.34; p=0.58, respectively). CONCLUSIONS: From 2002 to 2013, hospital admissions for AMI and stroke increased, whereas the unemployment rate decreased. However, the adjusted ARIMA model showed a positive association between unemployment rate and admissions due to AMI but not for stroke. Further studies are warranted to validate our findings and to better explore the mechanisms by which socioeconomic stressors, such as unemployment, might impact on the incidence of CVD.

Calculated and perceived cardiovascular risk in asymptomatic subjects submitted to a routine medical evaluation: The perception gap.

BACKGROUND: Poor adherence to medical treatment represents a major health problem. A subject's misperception of his own cardiovascular risk has been indicated as a key driver for low compliance with preventive measures. This study analysed the relationship between objectively calculated short- and long-term cardiovascular risk and its subjective perception. DESIGN: Cross-sectional study in asymptomatic Brazilian subjects. METHODS: Individuals (N = 6544, mean age 49.1 ± 7 years, 22.2% female) who underwent a routine mandatory health evaluation were studied. A questionnaire in which each individual rated his own cardiovascular risk as low, intermediate or high according to his own perception was used. The 10-year and lifetime cardiovascular risk were calculated respectively using the Framingham risk (FRS) and Lifetime risk (LRS) scores. Individuals were classified as hypo-perceivers (i.e. perceived risk lower than estimated risk), normo-perceivers (i.e. perceived risk coincident with estimated risk) and hyper-perceivers (i.e. perceived risk higher than estimated risk). RESULTS: Cardiovascular risk, using the FRS, was low in 77.9% (N = 5071), intermediate in 14.4% (N = 939) and high in 7.7% (N = 499) of subjects. Cardiovascular risk, using the LRS, was low in 7.6% (N = 492), intermediate in 43.1% (N = 2787) and high in 49.3% (N = 3184) of the study population. The prevalence of normo-perceivers was 57.6% using the FRS and only 20.6% using the LRS. Using the LRS, 72.3% of the intermediate and 91.2% of the high-risk subjects were hypo-perceivers. CONCLUSIONS: In a large sample of asymptomatic individuals, there was a gap between calculated and perceived cardiovascular risk. Using a long-term risk score, most of the intermediate- and high-risk subjects were hypo-perceivers.

Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.

BACKGROUND: Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients. DESIGN: Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45-59 years, and older, defined as 60-75 years) and exercise status (trained and untrained). METHODS: MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test. RESULTS: Exercise training significantly and similarly increased FBF and peak VO(2) in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients. CONCLUSION: Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.

Impact of gender on benefits of exercise training on sympathetic nerve activity and muscle blood flow in heart failure.

AIMS: We compared the effects of exercise training on neurovascular control and functional capacity in men and women with chronic heart failure (HF). METHODS AND RESULTS: Forty consecutive HF outpatients from the Heart Institute, University of Sao Paulo, Brazil were divided into the following four groups matched by age: men exercise-trained (n = 12), men untrained (n = 10), women exercise-trained (n = 9), women untrained (n = 9). Maximal exercise capacity was determined from a maximal progressive exercise test on a cycle ergometer. Forearm blood flow was measured by venous occlusion plethysmography. Muscle sympathetic nerve activity (MSNA) was recorded directly using the technique of microneurography. There were no differences between groups in any baseline parameters. Exercise training produced a similar reduction in resting MSNA (P = 0.000002) and forearm vascular resistance (P = 0.0003), in men and women with HF. Peak VO(2) was similarly increased in men and women with HF (P = 0.0003) and VE/VCO(2) slope was significantly decreased in men and women with HF (P = 0.0007). There were no significant changes in left-ventricular ejection fraction in men and women with HF. CONCLUSION: The benefits of exercise training on neurovascular control and functional capacity in patients with HF are independent of gender.

Increased muscle sympathetic nerve activity predicts mortality in heart failure patients.

BACKGROUND: Previous studies have associated neurohumoral excitation, as estimated by plasma norepinephrine levels, with increased mortality in heart failure. However, the prognostic value of neurovascular interplay in heart failure (HF) is unknown. We tested the hypothesis that the muscle sympathetic nerve activity (MSNA) and forearm blood flow would predict mortality in chronic heart failure patients. METHODS: One hundred and twenty two heart failure patients, NYHA II-IV, age 50+/-1 ys, LVEF 33+/-1%, and LVDD 7.1+/-0.2 mm, were followed up for one year. MSNA was directly measured from the peroneal nerve by microneurography. Forearm blood flow was obtained by venous occlusion plethysmography. The variables were analyzed by using univariate, stepwise multivariate Cox proportional hazards analysis, and Kaplan-Meier analysis. RESULTS: After one year, 34 pts died from cardiac death. The univariate analysis showed that MSNA, forearm blood flow, LVDD, LVEF, and heart rate were significant predictors of mortality. The multivariate analysis showed that only MSNA (P=0.001) and forearm blood flow (P=0.003) were significant independent predictors of mortality. On the basis of median levels of MSNA, survival rate was significantly lower in pts with >49 bursts/min. Similarly, survival rate was significantly lower in pts with forearm blood flow <1.87 ml/min/100 ml (P=0.002). CONCLUSION: MSNA and forearm blood flow predict mortality rate in patients with heart failure. It remains unknown whether therapies that specifically target these abnormalities will improve survival in heart failure.

Muscle sympathetic nerve activity in patients with Chagas' disease.

BACKGROUND: The progression of heart failure in Chagas' disease has been explained by remodeling, leading to neurohumoral activation, or by the direct parasite damage to parasympathetic neurons during acute phase, leading to early sympathetic activation and progressive heart failure. To help distinguish between these hypotheses we studied muscle sympathetic nerve activity (MSNA) at rest and during handgrip exercise (30% of maximal voluntary contraction) in patients with Chagas' disease and normal ejection fraction vs. patients with heart failure. METHODS: A consecutive study of 72 eligible out-patients/subjects was conducted between July 1998 and November 2004. The participants were classified in three advanced heart failure groups (New York Heart Association Functional Classes II-III): Chagas' disease (n=15), ischemic (n=15) and idiopathic cardiomyopathy (n=15). Twelve Chagas' disease patients without heart failure and normal ejection fraction, and 15 normal controls were also studied. MSNA was recorded directly from the peroneal nerve by microneurography technique. RESULTS: MSNA was greater in heart failure patients when compared with Chagas' disease patients without heart failure (51+/-3 vs. 20+/-2 bursts/min P=0.0001). MSNA in Chagas' patients with normal ejection fraction and normal controls was not different. During exercise, MSNA was similar in all 3 heart failure groups. And, was lower in the Chagas' patients with normal ejection fraction than in patients with Chagas' disease and heart failure (28+/-1 vs. 63+/-5 bursts/min, respectively). CONCLUSION: MSNA is not elevated in patients with Chagas' disease with normal ejection fraction. These findings support the concept of remodeling and neurohumoral activation as a common pathway following significant cardiac injury.

Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol.

BACKGROUND: Evidence suggests that carvedilol decreases muscle sympathetic nerve activity (MSNA) in patients with heart failure (HF) but carvedilol fails to improve forearm vascular resistance and overall functional capacity. Exercise training in HF reduces MSNA and improves forearm vascular resistance and functional capacity. AIMS: To investigate whether the beneficial effects exercise training on MSNA are maintained in the presence of carvedilol. METHODS AND RESULTS: Twenty seven HF patients, NYHA Class II-III, EF <35%, peak VO(2) <20 ml/kg/min, treated with carvedilol were randomly divided into two groups: exercise training (n=15) and untrained (n=12). MSNA was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The four-month training program consisted of three 60-min exercise/week on a cycloergometer. Baseline parameters were similar between groups. Exercise training reduced MSNA (-14+/-3.3 bursts/100 HB, p=0.001) and increased forearm blood flow (0.6+/-0.1 mL/min/100 g, p<0.001) in HF patients on carvedilol. In addition, exercise training improved peak VO(2) in HF patients (20+/-6%, p=0.002). MSNA, FBF and peak VO(2) were unchanged in untrained HF patients on carvedilol. CONCLUSION: Exercise training reduces MSNA in heart failure patients treated with carvedilol. In addition, the beneficial effects of exercise training on muscle blood flow and functional capacity are still realized in patients on carvedilol.

Evidências atuais dos benefícios do condicionamento físico no tratamento da insuficiência cardíaca congestiva / Evidences for the effects of physical training in the treatment of advanced heart failure

Insuficiência cardíaca é caracterizada por dispnéia e intolerância aos esforços, em decorrência de baixo débito cardíaco. Experiências acumuladas demonstram que o treinamento físico é seguro, representando uma importante conduta no tratamento da insuficiência cardíaca. Resultados recentes evidenciam que o treinamento físico diminui a atividade nervosa simpática muscular e melhora a função endotelial em pacientes com insuficiência cardíaca. Essas duas alterações provocam aumento expressivo da condutância vascular. Isso leva à redução das espécies reativas de oxigênio e, conseqüentemente, à diminuição dos níveis de citoquinas na musculatura esquelética. Em conjunto, o aumento da condutância vascular e a diminuição das citoquinas provocam melhora significativa da capacidade oxidativa muscular e, em última instância, da capacidade física de pacientes com insuficiência cardíaca. Entretanto, é necessário que o programa de treinamento físico seja adequado, conforme será apresentado nesta resenha.